Thoracic SMARCA4-deficient cancer descriptors and clinicopathologic determinants of survival: Analysis of a pooled database.

Abstract

9049 Background: Inactivation of SMARCA4, a catalytic subunit of the SWI/SNF complex, has been linked to high-grade aggressive cancers with poor prognoses. SMARCA4-deficient thoracic tumors (SDTT) can involve any part of the chest cavity, including the lungs, mediastinum, pleura, and chest wall. SDTT’s detailed clinical features and optimal treatment still need to be clarified. Therefore, we conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this unique group of thoracic cancers. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 120 cases of SDTT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 120 patients with confirmed SDTT were identified. The median age was 54, with a peak incidence between 56 and 68. There was a male preponderance with M:F of 3. The median duration of symptoms before diagnosis was 3.5 months. Patients presented with local disease in 11%, locally advanced in 21%, and metastases in 61%. The primary sites were the lungs (45%), mediastinum (42%), and pleura (13%). Common metastatic sites were bone (32%), adrenals (30%), liver (20%), Brain (20%), and lungs (18%). The median OS of the whole group was 6 months. Ninety percent of patients had a smoking history with a median of 26 pack-years. Histology comprised epithelioid/rhabdoid (79%) and carcinoma (adenocarcinoma, mucinous, and undifferentiated, 21%). Carcinomas had a better median OS than sarcomatous histology (11 vs. 6 months, p=0.03). Furthermore, early stages (N0/N1) had a superior median OS compared to advanced stages (N≥2, M+) (16 vs. 5 months, p=0.02). Compared to no treatment, local therapies (surgery (S) or radiation (RT)), combination chemotherapy (CT), and combined modalities (CT±S/RT) were statistically superior with a median OS of 1, 4, 6, and 11 months, respectively (p<0.0001). Further analysis revealed CT+S had superior median OS to CT+RT (16 vs. 9.5 months). Moreover, those with immune checkpoint inhibitors incorporated into their therapies had the best median OS outcomes (p<0.0001). Age, sex, primary site, and size did not impact OS. Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with SDTT cancers. It identifies the histologic type, stage, and treatment approach as critical determinants of OS.